Digital health interventions to promote healthy lifestyle in hemodialysis patients: an interventional pilot study

Low physical activity has been associated with poor prognosis in hemodialysis (HD) patients. Interventions to maintain healthy lifestyle in this population are important to reduce mortality. This study aimed to evaluate the effectiveness of digital health interventions (DHIs) for improving the physical activity and health-related quality of life (HRQoL) in HD patients. The 24-week prospective study enrolled 31 clinically stable HD patients. All participants were assigned home exercises and provided with wearable devices. Dietary and exercise information was uploaded to a health management platform. Suggestions about diet and exercise were provided, and a social media group was created. Physical performance testing was performed at baseline and during weeks 4, 8, 12, 16 and 24. HRQoL and nutritional status were evaluated. A total of 25 participants completed the study. After the interventions, the daily step count increased 1658 steps. The 10-time-repeated sit-to-stand test reduced by 4.4 s, the sit-to-stand transfers in 60 s increased 12 repetitions, the distance of six-minute walk test (6MWT) increased by 55.4 m. The mental health components and burden of kidney disease of the Kidney Disease Quality of Life survey, and subjective global assessment (SGA) scores improved. By Spearman correlation, the monthly step count correlated positively with 6MWT and SGA. DHIs that combined wearable devices, a health management platform, and social media could strengthen physical activity and improve the HRQoL and nutrition of maintenance HD patients. The results outline a new model to promote healthy lifestyle behaviors in HD patients.

End-stage renal disease (ESRD) has been increasing in recent decades.In Taiwan, the incidence and prevalence of ESRD is among the highest in the world 1 .The progression of chronic kidney disease (CKD) has an impact on the decrease in functional capacity in this vulnerable patient group 2 .People with ESRD often have other comorbidities such as hypertension, diabetes, and cardiovascular disease.Lifestyle modifications, including sufficient physical activity and adequate diet control are important for these chronic illnesses 3 .Low physical activity has been associated with poor prognosis in ESRD patients on hemodialysis (HD) 4,5 .Reductions in physical activity are significantly associated with poor prognosis and are independent of baseline physical activity 6 .Most HD patients are physically inactive, particularly on days when they undergo HD treatment 7 .
Engaging in physical activity is associated with decreased mortality risk among HD patients.The benefits of exercise in dialysis patients are well established, and support the prescription of physical activity in regular treatment 8 .Interventions to maintain physical activity in this vulnerable population are important.The Renal Exercise Demonstration Project in the United States showed that an initial lower physical component scale, on the Medical Outcomes Study Short-Form 36 questionnaire, could benefit more from exercise counseling in both objective measures and self-reported physical functioning 9 .A Japanese prospective cohort study found a substantial mortality benefit among HD patients whose physical activity comprised at least 4000 steps per non-dialysis OPEN 1 Renal Division, Department of Internal Medicine, National Taiwan University Hospital Yun Lin Branch, No. 579, Sec. 2, Yunlin Rd., Douliu, Yunlin County 640, Taiwan. 2 College of Medicine, National Taiwan University, Taipei, Taiwan. 3Department of Industrial Engineering and Management, National Yunlin University of Science and Technology, Douliu, Taiwan. 4Department of Dietetics, National Taiwan University Hospital Yun Lin Branch, Douliu, Taiwan. 5Department of Applied Foreign Languages, National Yunlin University of Science and Technology, Douliu, Taiwan. 6Cardiovascular Division, Department of Internal Medicine, National Taiwan University Hospital Yun Lin Branch, Douliu, Taiwan.* email: fongrong@ntu.edu.tw

Description of the intervention
The researchers included a nephrologist and her assistants, who were from graduate school of health industry management in National Yunlin University of Science and Technology.They were also supervised by physical therapists and dietitians.Each participant was provided with a wearable device (a Heart Rate Smart Wristband, GSH405-B6, Golden Smart Home Technology Corporation) (Fig. 1).The wristband was approved by the National Communications Commission of Taiwan (NCC verification code: CCAB16LP1430T3).The device could detect steps (0-120,000 steps, division 1 step), calories, and sleep periods.The wearable device was validated in previous studies 17,20 .
Each participant downloaded an app (WowGoHealth app) (Fig. 2) to connect with the health management platform (GSH AI health platform).Participants' exercise-related data, including number of steps walked, distance, consumed calories, and heart rate, were collected through the wearable devices.All participants were taught to record a dietary diary by taking photos of meals and using a smartphone application.All collected information was uploaded to the health management platform.Only the researchers could access the data on the health management platform.The researchers analyzed the pictures every day with average 3-5 pictures to calculate the calories and nutrients in the food, such as starches, proteins, and lipids, and the percentage of vegetables and fruits.The researchers made suggestions about diet to the participants.
Exercise included an 18-min calisthenics program made by the Health Promotion Administration, Ministry of Health and Welfare (Fig. 3).The video included stretching, aerobic and resistance training, and could be performed in a sitting or standing position.Participants were asked to perform the calisthenics at least three times

Secondary outcomes
HRQoL was measured by the Kidney Disease Quality of Life survey (KDQOL-36™) 28 .The KDQOL-36™ was a short form that includes the 12-Item Short Form Survey (SF-12) as a generic core plus the burden of kidney disease, symptoms/problems of kidney disease, and effects of kidney disease scales from the KDQOL-SF™ v1.3.Items 1-12 were SF-12; items 13-16 were burden of kidney disease; items 17-28 were symptoms/problems; while items 29-36 were effects of kidney disease.The higher the scores, the better the HRQoL.The Cronbach's alpha was estimated in excess of 0.8 28 .
The Subjective Global Assessment (SGA) was a reliable tool for the evaluation of nutritional status and for detection of protein-energy wasting (PEW) in dialysis patients 29 .The 7-point SGA scored according to the patients' history of weight change in the previous 6 months, dietary intake, and presence of gastro-intestinal symptoms (loss of appetite, nausea, vomiting, and diarrhea).A physical examination of loss of subcutaneous fat mass and muscle wasting was conducted.A score of 6-7 indicated a normal nutritional status, a score of 3-5 indicated mild to moderate PEW, and a score of 1-2 indicated severe PEW 30 .

Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics for Windows, version 22.0.0 (IBM Corporation), and a 2-sided P value < 0.05 was considered significant.We examined the distribution of all outcome data.The distributional properties of the data were expressed as mean ± standard deviation for continuous variables with a normal distribution or median (interquartile range) for those with a skewed distribution.The repeated measures ANOVA was used to compare the outcomes, and F test with Greenhouse-Geisser adjustment (F-GG) was used to correct the degrees of freedom of the F-distribution 31 .For categorical variables with percentages (%), a chi-square or Fisher's exact test was used.Pearson or Spearman correlation (normal or non-normal distribution, respectively) was used for analysis of association of monthly step count with the physical function, HRQoL, SGA, and laboratory data.

Ethics approval and consent to participate
The study is approved by National Taiwan University Hospital's Research Ethics Committee (No. 201812145RINA), and informed consent was acquired from all participants.The ClinicalTrials.govnumber was NCT05281497.The first trial registration was on 01/07/2019.

Baseline participant characteristics
Thirty-one participants completed the pretests.Six patients withdrew from the study (Fig. 5).A total of 25 participants completed the posttests.There were no dropouts caused by complications related to the intervention.The mean age of all participants was 54.0 years (standard deviation [SD] 12.9), and 56% were male.The baseline characteristics of these participants are presented in Table 1.The HD duration was 6.0 ± 6.1 years.Most of the participants had a senior high school degree (n = 11, 44%).Hypertension was the most prevalent comorbidity (96%), and 36% of participants had diabetes mellitus.Their body mass index was 23.6 ± 3.9 kg/m 2 .Their baseline serum albumin and hemoglobin levels were within the normal range.(212,037 ± 120,572) with an average of 7572.8 steps per day.By the end of the study, the monthly step count had increased by 46,437 steps compared with the baseline (P < 0.001), by an average increase of 1658 steps per day.The baseline STS-10 was 19.0 ± 5.6 s, and by week 4 was 14.5 ± 3.9 s, which represented much improvement (P < 0.001).At the end of the study, the STS-10 measurement was 4.4 s shorter than the baseline (P < 0.001).

Physical function (
The baseline STS-60 was 30.2 ± 9.9 times, and the STS-60 at week 4 was 39.3 ± 10.5 times, which represented a significant improvement (P < 0.001).The STS-60 at week 8 was 43.4 ± 12.5 times.This change was also significant compared with the STS-60 result from week 4 (P = 0.002).The values of STS-60 at week 12, 16 and 24 were similar.At the end of the study, the STS-60 measurement increased 12 times relative to the baseline (P < 0.001).The baseline 6MWT was 413.4 ± 65.8 m, and the 6MWT at week 4 was 455.6 ± 70.6 m, which demonstrated an improvement (P < 0.001).The 6MWT at week 8 reached a peak value (485.0 ± 73.4 m, P = 0.003).The 6MWT at week 12, 16 and 24 were similar, but better than the baseline data.At the end of the study, the 6MWT increased by 55.4 m compared with the baseline (P < 0.001).
The baseline HGS was 25.4 ± 11.2 kg for the non-dominant hand, and 27.0 ± 10.6 kg for the dominant hand.The baseline HGS of non-dominant hand was smaller than the HGS at week 12, 16 and 24.The baseline HGS of dominant hand was smaller than the HGS at week 4, 12, 16 and 24.Compared with baseline data, the nondominant hand and dominant hand HGS had increased by 2.2 kg and 1.9 kg, respectively, without statistical significance (P = 0.054, and P = 0.070, respectively) by the end of study.

Health-related quality of life and nutrition (Table 3)
The baseline scores of KDQOL-36™ are listed in Table 3.The scores of physical health components were similar throughout the 24 weeks.At week 4, the scores of mental health components, burden of kidney disease, symptoms and problems, and effects of kidney disease on daily life improved significantly.At week 8, only the score of symptoms and problems kept improving.But at week 12, the scores of mental health components, and symptoms and problems decreased significantly.At the end of study, the mental health components and burden of kidney disease showed improvement compared with baseline measurements significantly (P = 0.012, and P = 0.010, respectively).
The baseline SGA was 6.4 ± 0.6, which indicated normal nutritional status.Throughout the study, the SGA increased gradually, and the nutritional status was normal.At the end of the study, the SGA had increased 0.4 compared with the baseline (P = 0.015).4) During the study period, white blood count, hemoglobin and platelet count did not alter significantly.Serum glucose, albumin, uric acid, calcium, and phosphate levels fluctuated over time.At week 4, serum creatinine increased.At week 8, sodium reached the top.At the end of the study, the blood urea nitrogen (BUN) and potassium were elevated compared with the baseline (P < 0.002, and P = 0.001, respectively), possibly indicating more protein and potassium intake.

Spearman correlation
By Spearman correlation, the monthly step count moderately correlated positively with 6MWT (Spearman correlation coefficient Rs = 0.472, P = 0.017) (Table 5).The monthly step count of HD patients was directly proportional to the 6MWT distance.The monthly step count was not correlated with STS-10, STS-60 or handgrip measurements.STS-10 was highly correlated negatively with STS-60 (Rs = − 0.703, P < 0.01), and moderately correlated negatively with 6MWT (Rs = − 0.458, P = 0.021) and handgrip measurement.The monthly step count also moderately correlated positively with SGA (Rs = 0.438, P = 0.029) (Table 6); the higher the monthly step count, the higher the SGA was found, which indicated better nutritional status.The monthly step count was not correlated with HRQoL (Table 7) or laboratory data.The physical health components were strongly correlated negatively with burden of kidney disease (Rs = − 1.000, P < 0.01).

Discussion
In this study, the physical activity of 25 stable HD patients improved significantly after a 24-week intervention using wearable devices, a health-management platform, and social media.By the end of the study, the daily step count increased by 1658 steps, the STS-10 had shortened by 4.4 s, the STS-60 increased 12 repetitions, and the 6MWT increased by 55.4 m compared with the baseline.The metal health components and burden of kidney disease of HRQoL and nutritional status, measured by KDQOL-36™ and SGA, respectively, also improved significantly.By Spearman correlation, the monthly step count was correlated positively with the 6MWT distance and SGA score; the higher the monthly step count, the longer the 6MWT distance and higher SGA score were noted.
In one Spanish prospective study to determine the reliability of outcomes of physical performance tests for HD patients showed high intraclass correlation coefficients (≥ 0.88) for STS-10, STS-60, the one-leg heel-rise test, and the HGS test, suggesting good relative reliability 23 .The minimal detectable change scores at 90% confidence intervals (CI) were as follows: 8.4 s for the STS-10, 4 repetitions for the STS-60, 66.3 m for the 6MWT, 3.4 kg for HGS.Those degree of change was necessary to discriminate between the true effects of exercise interventions and the inherent variability of the cohort.In our study, only the improvement of STS-60 (increase 12 repetitions) reached the minimal detectable change score.It meant the change of STS-60 was due to an intervention.There were no relevant changes in HGS after our intervention.Some studies had similar results 32 .The exercise training was less focused on the upper limbs may explain these findings.
In the assessment of HRQoL, significant improvement of the mental components and burden of kidney disease were observed.The participants felt less depressed, less frustrated, and they were not the burdens of family.Unlike the secondary analysis of the EXCITE trial 33 , which revealed cognitive function in the Kidney Disease Quality of Life-Short Form significantly reduced in patients of the control arm, while it remained substantially unchanged in those of the active arm.Because the tools in evaluation of HRQoL were different, the beneficial effects of exercise were diverse.

Types and doses of physical activity
A systematic review and meta-analysis of exercise interventions for ESRD patients on HD or peritoneal dialysis (from 27 studies with 1156 participants) showed that exercise, regardless of modality, improved objective measures of physical activity, such as increased 6MWT distance, sit-to-stand time or repetitions, and grip strength as well as step and stair climb times or repetitions, dynamic mobility, and short physical performance battery scores 12 .Another systematic review with network meta-analysis showed that the combined training (aerobic plus resistance training) was the most effective modality for increasing aerobic capacity and blood pressure control in HD patients 34 .Compared with data from one of the largest randomized control trails in the area with 296 participants, the exercise group experienced a 6-month personalized walking exercise program and demonstrated an improvement of 39 m in 6MWT and HRQoL in subscales of cognitive function and social interaction 35 .Our intervention of wearable device-based walking comprised aerobic exercise, and the calisthenics included stretching, aerobic and resistance training.These home-based exercises could improve cardiopulmonary endurance and flexibility, and achieve long-term effects in a safe way.
A daily step count goal of 7500 steps was set according to a prospective cohort study of 18,289 women in the United States which displayed survival benefits 36 .A prospective Japanese cohort study found a substantial mortality benefit among the disability-free HD patients who engaged in at least 4000 steps per day 10 .This provided a basis for a minimum initial recommendation that kidney health providers could provide for stable HD patients.Another retrospective cohort study was performed in 192 Japanese HD patients with a 7-year follow-up; a mortality of 20.8% was noted 6 .The average number of steps taken per non-dialysis day was used as a measure of physical activity (about 4421 ± 3048 steps).The patients were divided into three categories according to the percentage changes in physical activity between baseline and 12 months.The hazard ratio on multivariate analysis in patients with decreased physical activity (> 30% decrease) was 3.68 (95% CI 1.55-8.78;P = 0.01) compared to those with increased physical activity (> 30% increase).Reductions in physical activity were significantly associated with poor prognosis and were independent of patient characteristics and baseline physical activity.Therefore, improved prognosis in HD patients required the means of preventing a decline in physical activity over time.Compared with this pedometer-guided exercise study, the daily step count tracked by our participants exceeded expectations, from an average 5469 steps per day at baseline to 7127 steps per day by the end of the Table 7. Spearman correlation of steps per month and health-related quality of life.*P < 0.05, **P < 0.01.

Effects of kidney disease on daily life
Steps study.The daily step count did not exceed that of the general population and may be related to inactivity during HD therapy.The trend of increased step count suggested the effectiveness of this new model of telehealth.The 2015 Taiwan Chronic Kidney Disease Clinical Guidelines 37 encourage physical activity compatible with cardiovascular health and tolerance, and aim for at least 30 min activity five times per week.The NICE clinical practice guidelines about exercise and lifestyle emphasize physical activity and exercise in the HD population where there are no contraindications 11 .HD patients were recommended to aim for 150 min of moderate intensity activity or 75 min of vigorous activity a week, or a mixture of both as per the UK Chief Medical Officers' Guidelines.This may include a combination of interdialytic and intradialytic exercise 38 .The best protocol for CKD patients including maintenance HD patients remains to be established 39 .Most studies focused on intradialytic exercise, and some studies included independent home exercise 32,33,38 .Wearable devices were used along with a remote-control model via a health management platform.The exercise program with only walking and calisthenics at least three sessions per week appeared easy to implement in clinical practice with high attendance among participants.

Design of the telehealth from digital health interventions (DHIs)
As in our previous randomized controlled study, wearable devices were applied, with a health management platform, and social media support for 12 weeks to people diagnosed with CKD stage 1-4.The intervention group gained significantly higher scores for self-efficacy and self-management.HRQoL and the daily step counts increased in the intervention group.The decline in eGFR were significantly slower in the intervention group (− 0.56 vs. − 4.58 mL/min/1.73m 2 ).These results outlined a new self-management model to promote healthy lifestyle behaviors in CKD patients 17 .In the present investigation, a longer-term intervention was performed to maintenance HD patients, and it was documented that their physical function and HRQoL improved.A randomized control trial was not performed because all participants should be encouraged to pursue healthy habits.This study also provided a new model for promoting sustainable healthy lifestyles in stable HD patients.
In a cross-sectional observational study, 44% of HD patients did not believe they had an important role in managing their health.The average patient activation-score by Patient Activation Measure-13 was 51 (0-100), which was lower than other chronic patient groups.Multiple linear regression showed that older patients, who reported being in bad health, treated in a particular hospital, without leisure-time activities, and living in a residential care home, had a lower patient activation level 40 .Our participants were younger than the general HD population.They were more motivated to increase physical activity and strengthen self-management.As the mean age of people undergoing dialysis therapy has increased, the importance of maintaining the functional capacity and increasing physical activity should be emphasized.
DHIs were used in the HD field mostly for dialysis service management, dialysis procedure, anemia management, and arteriovenous fistula assessment 41 .This interventional study is unique in the combination of a wearable device, a health management platform, and social media in a population under regular HD.Few studies have adopted wearable devices, a health management platform, and social media to quantify motor performance with immediate feedback to empower participants 42 .Suggestions were provided to the participants according to uploaded images of their diet, so they could adjust their diet.Our intervention type is a multifactorial behavior modification which includes exercise and diet.During a global pandemic such as coronavirus (COVID-19), telemedicine is a trustworthy method of clinical practice to limit travel and exposure and encourage social distancing while inspiring care from healthcare providers.The use of new technology is a practical way to deliver health care and increase interactions between medical staff and HD patients.However, it requires technological literacy among the patient population.More investigations are needed into the potential effects of DHIs on health promotion and lifestyle in HD patients, and even in patients receiving peritoneal dialysis or post-renal transplantation.

Limitations
Participants in this study were recruited from a teaching hospital and a HD center of central Taiwan.Participants were younger than the general HD population in Taiwan, so the results could not be used among the general HD population.The sample was relatively small due to a lack of motivation among participants.The small sample size may have amplified the differences before and after the intervention.Although physical activity and HRQoL outcomes improved after the 24-week intervention, the long-term effects of the intervention should also be further evaluated.A follow-up period of at least 1-3 years would allow for better evaluation of the long-term effectiveness, such as cardiovascular outcome and mortality.No control group was included in this analysis, making it impossible to understand whether the improvements were due to the intervention or not.Finally, our intervention design meant that we could not distinguish between the effects of exercise, dietary intervention, or emotional support via social media.

Conclusion
DHIs that combined wearable devices, a health management platform, and social media could strengthen physical activity and improve the HRQoL and nutrition of maintenance HD patients.The results outline a new model that can promote healthy lifestyle behaviors as part of routine care in HD patients.

Figure 2 .
Figure 2. User interface of the health management platform software (WowGoHealth App).

Figure 4 .
Figure 4. CAMRY digital hand dynamometer EH101 was used to measure the hand grip strength developed by each hand.

Figure 5 .
Figure 5. Flow chart of this study.

Table 2 )
Monthly step counts were non-normally distributed, and the median of baseline monthly steps were 123,115 (interquartile range 102,458-181,744, average daily steps 4397).Monthly step counts increased from 153,120 ± 61,635 steps (daily steps counts 5468.6 ± 2201.3 steps) to 209,988 ± 115,986 steps (daily steps counts 7499.6 ± 4142.4 steps) within the first 4 weeks (P < 0.001).The monthly step-counts reached a peak in week 8